Protein Restriction & Liver Hormones: Appetite, Brain, Behavior | Chris Morrison | 251
The effects of protein restriction on metabolism, liver hormones, brain, and behavior.
Episode Summary: Dr. Christopher Morrison talks about how animals sense and prioritize nutrients like protein, discussing defense mechanisms for essentials such as oxygen, water, sodium, and energy; the brain’s role in detecting protein deprivation via signals like FGF21; trade-offs between growth, reproduction, and longevity under protein restriction; and reconciling high-protein diets for satiety and muscle maintenance with low-protein benefits for metabolic health and lifespan extension.
About the guest: Christopher Morrison, PhD is a professor and researcher at the Pennington Biomedical Research Center in Baton Rouge, Louisiana, where he has worked for over 22 years focusing on nutrition, metabolism, and chronic diseases like obesity and diabetes.
Discussion Points:
The body prioritizes nutrients hierarchically: oxygen and water first, then sodium, energy, and protein, with weaker defenses for carbs or fats.
Animals develop specific appetites for deprived nutrients, like salt or protein, often through post-ingestive learning rather than just taste.
Protein restriction (e.g., 5% vs. 20% in diets) increases food intake and energy expenditure in mice to maintain protein levels, even at the cost of extra calories.
FGF21, a liver hormone, signals protein deprivation to the brain (via NTS region), driving protein-seeking behavior and metabolic changes; it’s essential for low-protein responses.
Protein restriction extends lifespan in lab animals by suppressing growth signals like IGF-1 and mTOR, but may impair immunity or wound healing in real-world conditions.
High protein aids satiety, weight loss, and muscle building, but overconsumption may shorten lifespan; optimal intake depends on age, activity, and goals (e.g., not for pregnant or elderly).
No one-size-fits-all for protein: mild restriction may benefit middle-aged sedentary people for health, while athletes need more; balance avoids excesses.
*Not medical advice.
00:00:00 Intro
00:06:10 Nutrient Detection & Adequacy
00:11:11 Fluid & Sodium Defenses
00:16:20 Protein vs Other Macronutrients
00:21:21 Post-Ingestive Learning & Flavors
00:26:34 Hyperphagia on Low Protein
00:31:10 Restriction Effects on Growth
00:36:33 Longevity & Restriction Trade-Offs
00:41:47 Behavioral Changes & Choices
00:46:44 Preference in Choice Experiments
00:53:44 Innate vs Learned Appetite
00:58:39 Protein Digestion & Signals
01:04:40 FGF21 in Fasting & Restriction
01:10:40 FGF21 Knockouts & Relevance
01:15:20 Brain Receptors & Sites
01:20:49 Growth & Longevity Trade-Offs
01:25:04 High Protein Satiety & Muscle
01:30:33 FGF21 Scaling & Future Work
01:35:39 Final Thoughts & Recommendations
3 Comments
1:23: I'm so glad he mentioned the competing drives of reproduction vs longevity. I've suspected that to be the case for a long time, and agree that longevity does not equal a high quality of life. Following Bryan Johnson has reinforced my hypothesis. Don't get me wrong– he seems like a happy guy, but I worry about his very restricted vegan diet, collagen notwithstanding. He looks quite blood-deficient, and his body temperature is lower than mine was when I was severely emaciated years ago. I hope his health stays stable. This was a great interview.
Great interview!
It's always tricky to believe in diet intervention studies were half of them use seed oils as fat– I always get the impulse to ask: which fats, exactly?
All M&M content is available on Substack. Podcast, writing, free weekly newsletter:
[ https://mindandmatter.substack.com ]
If you enjoy M&M content and want to provide further support, read this:
[ http://tiny.cc/supportmm ]